rs7868111

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000093.5(COL5A1):c.4955-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,488,796 control chromosomes in the GnomAD database, including 374,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38841 hom., cov: 33)

Exomes 𝑓: 0.71 ( 335731 hom. )

Consequence

COL5A1
NM_000093.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.28

Variant links:

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 links:

LOC101448202 (HGNC:):

LOC101448202 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-134825764-T-C is Benign according to our data. Variant chr9-134825764-T-C is described in ClinVar as [Benign]. Clinvar id is 255092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.4955-28T>C	intron_variant	Intron 62 of 65	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.4955-28T>C	intron_variant	Intron 62 of 65		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.4955-28T>C	intron_variant	Intron 62 of 64		XP_016869755.1
LOC101448202	NR_103451.2 link	n.71-5555A>G	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL5A1	ENST00000371817.8 link	c.4955-28T>C	intron_variant	Intron 62 of 65	1	NM_000093.5	ENSP00000360882.3	P20908-1
COL5A1	ENST00000371820.4 link	c.4955-28T>C	intron_variant	Intron 62 of 65	2		ENSP00000360885.4	P20908-2H7BY82
COL5A1	ENST00000460264.5 link	n.423-28T>C	intron_variant	Intron 3 of 4	3
COL5A1	ENST00000465877.1 link	n.135-28T>C	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.714

AC:

108617

AN:

152074

Hom.:

38816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.856

Gnomad AMR

AF:

0.674

Gnomad ASJ

AF:

0.785

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.697

Gnomad OTH

AF:

0.710

GnomAD3 exomes

AF:

0.720

AC:

179176

AN:

248800

Hom.:

64616

AF XY:

0.726

AC XY:

97720

AN XY:

134560

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.661

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.778

Gnomad SAS exome

AF:

0.793

Gnomad FIN exome

AF:

0.721

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.712

GnomAD4 exome

AF:

0.708

AC:

945974

AN:

1336604

Hom.:

335731

Cov.:

AF XY:

0.710

AC XY:

477090

AN XY:

671614

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.665

Gnomad4 ASJ exome

AF:

0.785

Gnomad4 EAS exome

AF:

0.732

Gnomad4 SAS exome

AF:

0.790

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.698

Gnomad4 OTH exome

AF:

0.714

GnomAD4 genome

AF:

0.714

AC:

108690

AN:

152192

Hom.:

38841

Cov.:

AF XY:

0.718

AC XY:

53389

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.729

Gnomad4 AMR

AF:

0.675

Gnomad4 ASJ

AF:

0.785

Gnomad4 EAS

AF:

0.763

Gnomad4 SAS

AF:

0.807

Gnomad4 FIN

AF:

0.723

Gnomad4 NFE

AF:

0.697

Gnomad4 OTH

AF:

0.709

Alfa

AF:

0.666

Hom.:

4084

Bravo

AF:

0.715

Asia WGS

AF:

0.786

AC:

2729

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fibromuscular dysplasia, multifocal

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome, classic type, 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.37

DANN

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over